A viable transparent corneal model can provide the basis for studying novel ophthalmic drugs and new gene delivery approaches. Moreover, there is currently a clinical need for improved understanding of corneal wound-healing mechanisms in order to solve corneal haze problems associated with LASIK procedures and outcomes in corneal transplants. An understanding of the factors that contribute to the expression of the wound healing phenotype in the cornea can lead to an understanding of how to control these changes. The proposed research aims to understand and control protein expression in corneal keratocytes in order to achieve the quiescent transparent phenotype in our tissue-engineered constructs. Our research design approaches this work from three directions;one approach investigates the effect of stromal cells grown in collagen scaffolds co-cultured with corneal endothelial cells, another approach looks at the effect of the microstructure of the matrix that the cells are grown in, while the third approach assesses the effects of mechanical stress on the growing tissue construct. All of these factors are present in the natural cornea and represent normal signals to corneal keratocytes. PUBLIC HEALTH RELEVANCE: The proposed research seeks to create viable, transparent corneal tissue that can serve as replacement tissue for diseased or damaged human corneas. An artificially created transparent cornea can address the need for corneal tissue transplants due to donor shortages, and would provide a model in which to study the effects of new ophthalmic drugs and laser treatments for vision correction.